This phase I/II trial is studying the side effects and best dose of bendamustine hydrochloride when given together with idarubicin in treating older patients with previously untreated acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Drugs used in chemotherapy, such as bendamustine hydrochloride or idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells

The highest dose level at which no more than one patient out of 6 experiences dose-limiting toxicities (DLT). DLT consists of grade 3-4 non-hematologic toxicity, with the exception of drug-related fever; alopecia; anorexia; inadequately treated nausea, vomiting, and/or diarrhea; and grade 3/4 increase in ALT, AST, or bilirubin that recovers to < grade 2 by 7 days.

Incidence of greater than or equal to grade 3 toxicity [ Time Frame: Through day +100 after end of therapy or until the patient received an alternative treatment for leukemia, whatever happens earlier ] [ Designated as safety issue: Yes ]

Toxicities will be graded using the National Cancer Institute (NCI) Common Toxicity Criteria version 3.0.

Patients receive bendamustine hydrochloride IV on days 1-5 and idarubicin IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Drug: bendamustine hydrochloride

Given IV

Other Names:

bendamustin hydrochloride

bendamustine

cytostasan hydrochloride

Treanda

Drug: idarubicin

Given IV

Other Names:

4-demethoxydaunorubicin

4-DMDR

DMDR

IDA

Detailed Description:

PRIMARY OBJECTIVES:

I. The maximum tolerated dose (MTD) that is associated with a complete remission (CR) rate of at least 40%, and a rate of grade 3-4 extramedullary toxicity < 30% in patients aged 50 or older with previously untreated AML or high-risk MDS.

SECONDARY OBJECTIVES:

I. The disease-free survival (DFS), and overall survival (OS) after therapy at each level of the dosing strategy.

OUTLINE: This is a phase I, dose-escalation study of bendamustine hydrochloride followed by a phase II study.

Patients receive bendamustine hydrochloride intravenously (IV) on days 1-5 and idarubicin IV on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then annually thereafter for 3 years.

Eligibility

Ages Eligible for Study:

50 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Diagnosis of untreated AML or MDS with 10-19% marrow blasts; patients may be enrolled if they received prior treatment with demethylating agents specifically for the purpose of treating MDS or if they have received a single dose of cytarabine for the control of symptoms related to AML

Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent

Males should be willing to use an effective contraceptive method during the study and for a minimum of 6 months after study treatment

Women must be postmenopausal or must be willing to use an acceptable method of contraception to avoid pregnancy for the entire period of the study and for at least 3 months after the study; a postmenopausal woman is defined as a woman who has experienced amenorrhea > 12 consecutive months or a woman on hormone replacement therapy with documented follicle-stimulating hormone (FSH) level > 35 mIU/mL; for patients in whom menopausal state is in question, a negative pregnancy test will be required prior to enrollment

Exclusion Criteria:

Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol

Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea or single-dose cytarabine; subjects who are enrolled with high risk MDS (specifically) may have prior treatment with drugs in the class called "demethylating agents"; examples of these drugs include 5-azacytidine (azacitidine) and 5-azadeoxycytidine (decitabine), and may include approved or experimental drugs not currently used, which fall into this class and may be developed in the future; the patient must have recovered from all acute toxicities from any previous therapy

Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment

Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)

Known hypersensitivity to bendamustine (bendamustine hydrochloride) or idarubicin

Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF)

Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy

Other circumstances in which patients with prior malignancies are not excluded, include the following:

Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, if definitive treatment for the condition has been completed

Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values if hormonal therapy has been initiated, or a radical prostatectomy or definitive radiotherapy has been performed

Concurrent hormonal therapy is allowed

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01141725